This investigation was performed to evaluate the impact of lyophilized pomegranate peel nanoparticles (LPPNPs) as an antioxidant and antimicrobial in meatballs during storage at 4 ± 1 °C up to 15 days. LPP-NPs were incorporated into freshly minced beef meat at 1 and 1.5% and compared with 0.01% butylated hydroxytoluene (BHT) as a reference and control sample (without antioxidant). The LPP-NPs showed a high phenolic content and antioxidant capacity. In LPP-NPs-treated samples, contents of peroxide, thiobarbituric acid reactive substances (TBARS), and total volatile base nitrogen (TVB-N) were lower than the control (over 15 days). Cooking characteristics in meatball including LPP-NPs were improved during the storage. The microbial load of samples treated with LPP-NPs was lower than the control during storage. Sensory evaluation of color and rancid odor in treated meatballs were accepted with a high score up to 15 days. The results demonstrated that LPP-NPs were more effective in retarding lipid oxidation, improving the microbial quality, and cooking characteristics of meatballs.